ArticleBMC genomics2015
Identification of pneumococcal colonization determinants in the stringent response pathway facilitated by genomic diversity.
Article in BMC genomics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 14 citations in OpenAlex.
- The metabolic, microbial and immunological demands of pneumococcal colonisation.PLoS pathogens · 2025Review
- Diverse regulatory pathways modulate bet hedging of competence induction in epigenetically-differentiated phase variants of Streptococcus pneumoniae.Nucleic acids research · 2023Article
- Article
- A molecular link between cell wall biosynthesis, translation fidelity, and stringent response inProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Regulation of (p)ppGpp and Its Homologs on Environmental Adaptation, Survival, and Pathogenicity of Streptococci.Frontiers in microbiology · 2020Review
- miRNAs and Novel Food Compounds Related to the Browning Process.International journal of molecular sciences · 2019Review
- Genomic Epidemiology of Penicillin-Nonsusceptible Pneumococci with Nonvaccine Serotypes Causing Invasive Disease in the United States.Journal of clinical microbiology · 2017Article
- Interacting networks of resistance, virulence and core machinery genes identified by genome-wide epistasis analysis.PLoS genetics · 2017Article
- Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundUnderstanding genetic determinants of a microbial phenotype generally involves creating and comparing isogenic strains differing at the locus of interest, but the naturally existing genomic and phenotypic diversity of microbial populations has rarely been exploited. Here we report use of a diverse collection of 616 carriage isolates of Streptococcus pneumoniae and their genome sequences to help identify a novel determinant of pneumococcal colonization.
resultsA spontaneously arising laboratory variant (SpnYL101) of a capsule-switched TIGR4 strain (TIGR4:19F) showed reduced ability to establish mouse nasal colonization and lower resistance to non-opsonic neutrophil-mediated killing in vitro, a phenotype correlated with in vivo success. Whole genome sequencing revealed 5 single nucleotide polymorphisms (SNPs) affecting 4 genes in SpnYL101 relative to its ancestor. To evaluate the effect of variation in each gene, we performed an in silico screen of 616 previously published genome sequences to identify pairs of closely-related, serotype-matched isolates that differ at the gene of interest, and compared their resistance to neutrophil-killing. This method allowed rapid examination of multiple candidate genes and found phenotypic differences apparently associated with variation in SP_1645, a RelA/ SpoT homolog (RSH) involved in the stringent response. To establish causality, the alleles corresponding to SP_1645 were switched between the TIGR4:19F and SpnYL101. The wild-type SP_1645 conferred higher resistance to neutrophil-killing and competitiveness in mouse colonization. Using a similar strategy, variation in another RSH gene (TIGR4 locus tag SP_1097) was found to alter resistance to neutrophil-killing.
conclusionsThese results indicate that analysis of naturally existing genomic diversity complements traditional genetics approaches to accelerate genotype-phenotype analysis.
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